A central problem in cancer research is determining the structure of membranes in normal and tumor cells. Conventional transmission and scanning electron microscopy investigations in a number of laboratories are contributing to our knowledge of cell surface characteristics, but it is clear that fresh approaches are also needed. The purpose of this research project is to develop and apply a new kind of microscopy, specifically designed to examine chemical differences in cell surfaces and other membranes. This technique, photoelectron microscopy, utilizes differences in photoelectron quantum yields to visualize the biological surfaces. The escape depth of the electrons is extremely short, which permits mapping of membrane surfaces without interference from the cytoplasmic contents of the cell. The mechanism of contrast is entirely different from transmission and scanning electron microscopy, and it is possible to visualize different biochemical features. In previous grant periods, the feasibility of this approach has been experimentally verified, the first photoelectron images ever seen of biological samples have been reported and the photoelectron quantum yields of the major classes of cell surface components have been determined. Recently a new ultrahigh vacuum photoelectron microscope has been constructed and it was shown that this technique can also detect chemical carcinogens such as benzo(a)pyrene. The major goals for this coming year include examining cell surface topography by photoelectron microscopy (gold-palladium coated mouse 3T3 cells and chick embryo fibroblasts), analyzing the various factors contributing to the depth of information in this technique, and completing studies of the photoelectric properties of fluorescent dyes used in immunological assays. The instrumental goals focus on designing a new low temperature stage for the photoelectron microscope.